1. Field of Invention
The present invention relates generally to the field of radiotherapy treatment systems. More specifically, the present invention is related to application of modulated x-rays.
2. Discussion of Prior Art
U.S. Pat. No. 5,044,006, entitled MICROWAVE FREQUENCY MODULATION OF X-RAY BEAM FOR RADIO THERAPY TREATMENT SYSTEM, commonly invented (Cyrulnik), issued on Aug. 27, 1991, and hereby incorporated by reference, discloses a method and apparatus for producing an x-ray beam modulated at a microwave frequency for absorption by pathological materials including macromolecules, such as oncogenes, for the radiological therapeutic treatment of tumors and other pathological conditions. As disclosed by Cyrulnik, the atomic structure of certain macromolecules (molecules having a backbone structure of 20,000 or more atoms) suggests that such molecules may have a “signature” frequency for resonant energy absorption. In the system of Cyrulnik, an x-ray beam is amplitude modulated at a predetermined or empirically determined microwave frequency equal to a resonant interactive frequency for a selected pathological material. Sufficient x-ray energy may be supplied, for example, in order to destroy the pathological material.
The teachings of the U.S. Pat. No. 5,044,006 patent are best understood with the following discussion of the technology in conjunction with original FIGS. 2 and 6 of the '006 patent (herein FIGS. 1 and 2):
1. Molecular Orbitals
The energy of an electron in orbit must be sufficient to counterbalance the attracting electromagnetic force maintaining it in orbit, which, like gravitational force, varies inversely with the square of its distance to the center of attraction, that is, the size of the orbit. The energy absorbed in a transition between adjacent orbitals therefore varies inversely with the difference in the squares of these distances, which are close to each other in value being adjacent:a2−b2=(a−b)(a+b)which approximates a constant×a, so that the energy absorbed is inversely proportional to the size of the orbital.2. DNA
Deoxyribonucleic acid, the genetic material of which the chromosomes of human cells are composed, consists of pairs of macromolecules containing a backbone of units of 5 carbon atoms linked by phosphorous and oxygen atoms and each with a side chain of a purine or pyrimidine base. Viruses and genes that cause cancer (oncogenes) consist of such macromolecules with lengths on the order of 4,000 base pairs, or a backbone of some 20,000 atoms.
3. Resonant Frequency
The lowest transitions of electron orbitals in single atoms result in absorption of visible light, which has a frequency about 4(1014) cycles per second (cps). As previously explained, and as can be shown rigorously, the frequency of absorption by the lowest transition of molecular orbitals varies inversely with the size of the molecule.
A molecule 20,000 base pairs in length, each containing a string of 8 atoms per set of exons and introns, would therefore be expected to absorb radiation at a frequency of:[1/(8·2)](1/2·104)(4·1014) =4/32·1010=1.25·109 cpswhich is in the microwave range.4. Penetration by Modulation
The principle used extensively in radio and television transmission of modulating a carrier wave by one of considerable different frequency can be utilized to overcome the difficulty of delivering selectively-absorbable radiation with destructive potential to oncogenes. When the carrier wave is modulated by a signal containing a square wave component such as occurs when it is generated by a device that is turned on and off at the modulating frequency, then radiation with components at both frequencies results, so that resonant absorption of the compound carrier wave can take place. In this way, if an x-ray beam is turned on and off at a resonant microwave frequency, it can act as a carrier wave to allow penetration of the microwave frequency energy to its otherwise inaccessible target, and at the same time be selectively absorbed by macromolecules such as oncogenes whose resonant frequency of absorption is tuned to the frequency of modulation of the x-ray beam by the microwave frequency.
This can be accomplished by interposing a klystron or similar device in the high voltage circuit of the x-ray generating tube, which will turn the beam on and off at microwave frequencies.
5. Detection
To determine when absorption is occurring and by which structures without having to empirically destroy tissue by trial and error, modulate the x-ray beam of a CAT scanner with a klystron or similar device. A CAT scanner detects the absorption of a standard low radiation level diagnostic x-ray beam at any point inside the body by dividing that beam so that it is viewed from several angles.
If this is done over the spectrum of frequencies of possible absorption by oncogenes, then at those frequencies which are absorbed by the genetic material unique to the tumor or malignancy, that tissue, and that tissue alone, will show up as absorbent on the scan.
The spectrum of microwave frequencies can be impressed on the scanner's x-ray beam at each angle during the course of a single scan by systematically varying the klystron frequency. Since absorption occurs in 10−9 seconds, the electron beam, which has a single target dwell time of 100 microseconds, can accommodate 10−4/10−9=105 different microwave frequencies of modulation. Thus, each of the 30,000 or so human genes could be tested for unique absorption at 3 frequencies in one scan, allowing for allelic mutation.
A scan would be generated from memory for each frequency by sampling the detector output at any particular time delay after the initiation of the beam. Each absorbing structure, such a tumor, would “light up” when its resonant frequency is selected.
Although only a small portion of the x-ray beam is utilized at any given modulating frequency, this is sufficient to produce the same intensity of absorption as is seen on an ordinary CAT scan, as will be shown in the next section.
6. Safety
In an ordinary plain skull x-ray series (which contains the same dose of radiation as a CT scan), approximately 3% of the x-ray beam is absorbed in total, of which the brain absorbs 1%. This 3/10,000 of the beam is absorbed by a column of cells given by the cube root of the number of cells in the roughly spherical brain, which total 3(1010), their cube root being about 3000.
If, instead of the type of absorption seen in a spectrophotometer where each subsequent unit absorbs the same proportion of the beam, the entire beam is absorbed by a single cell, then in order to absorb the same amount of radiation as in an ordinary CT scan (and thus in an ordinary skull x-ray), a single cell would have to absorb 1/3000 of the 3/10,000 of the beam which is 1/107. The duty cycle of modulation limits to this maximum the absorbable radiation at each frequency of modulation of the x-ray beam during imaging.
Therefore, even though each resonant cell absorbs the entire available beam at that frequency, it absorbs no more than would be absorbed from an ordinary plain film, yet it absorbs 3000 times as much as other cells and 30 times as much as bone, allowing safe but effective detection by CT.
7. Treatment
Once the unique frequency of absorption of the modulated x-ray beam has been determined as noted above, selective destruction of undesirable structures such as oncogenes or their RNA transcripts, viruses, or other macromolecular nucleic acid configurations can be accomplished by scanning the patient a second time, this time with the klystron tuned to the unique resonant frequency of absorption throughout the duration of the x-ray beam. In this way the duty cycle during absorption is increased by a factor of approximately 109. (Before, it was turned on 109 times per second, each time at a different frequency; now each of the 109 times occurs at the single unique resonant absorbed frequency). Even if every cell of one of the several cell types in the brain were malignant, the increased dosage at full duty cycle of a factor of 109 of radiation specifically to those cells, each absorbing 3000 times the radiation that it would in a conventional skull x-ray series or Cr scan, would be sufficient to eliminate or deimmortalize them all. In practice, a tumor becomes symptomatic at a cell volume of approximately 105 cells, so that the effective dosage delivered to such a tumor would be equivalent to 3000(109)(10−5)=3(107) rads per cell (the total radiation dose in a CAT scan being on the order of a rad), which is 3000 times the curative maximum dosage used in radiotherapy, with the significant difference being that in this case the dosage delivered to the rest (nonmalignant) of the cells which do not absorb is still only one additional rad for this second scan, so that the treatment would be safe to normal cells.
In conventional radiation therapy, however, lethal tumor dose of 5000 rads represents a total, each cell only absorbing 1/105 of this (or, in the case of neoplastic cells a somewhat greater multiple of the same order of magnitude) i.e. about 1/10 of a rad. With the proposed technique, this can be multiplied 105 fold, which would easily destroy the tumor, even if repair is allowed for. Fractionation of the 5000 rads into 200 rad doses to minimize radiation damage to other tissues can be obviated, minimizing repair of the tumor cells.
The net lethal effect on target tissue of the proposed technique is on the order of 100 times that of conventional radiotherapy, whereas radiation exposure of nontargeted tissue is 3000 times less than a diagnostic x-ray series.
Of course, with the disclosed technique the dose can also be fractionated by reducing the duty cycle if 100 times the lethal tumor dose is not needed, depending on the clinical situation such as the size of the tumor. Higher doses can also be achieved if desired by repeating the scan at full duty cycle, each repetition doubling the dose to the malignancy with negligible additional radiation to healthy tissue. Furthermore, once the unique frequency of resonant absorption is determined using the CT scanner, the klystron or other modulating device can be connected to conventional x-ray equipment, whether a simple diagnostic x-ray tube or radiotherapy equipment, in order to modulate its beam so as to achieve a more rapid treatment session than with a CAT scanner.
It should be noted that, unlike other techniques which selectively target tissue in a spatial manner by limiting radiation to a small area at the site of the tumor, the disclosed technique, though highly selective against undesirable tissue, is not limited in space, and can thus destroy those malignant cells outside the main tumor bulk which are responsible for recurrence, failed surgery, and metastasis. In principle, I.Y.H. this technique could be used in a total body fashion to cure metastatic malignancy because of its high selectivity and consequent high safety factor and effectiveness.
Furthermore, since the detection process is empirical, determining solely which frequency is uniquely absorbed by the malignancy, it does not depend on the cause(s) of cancer; as long as there is an abnormal genetic configuration unique to the tumor, even if it also involves loss of inhibition by an inactivated or abnormally absent gene, the change in that length of the DNA molecule being transcribed by the chromosome should result in a unique pattern of absorption with consequent destruction of the tumor by the radiation.
8. Equipment
Disclosed is the concept of producing selective elimination of undesirable entities by achieving resonant absorption of penetrating radiation by their macromolecules of specific configuration, such as oncogenes and viruses, by means of modulation of the radiation at that resonant frequency whose unique absorption is determined in a safe manner using computerized tomography (CT). The method of achieving unique absorption of high energy radiation by modulating at the resonant frequency was an innovation in this proposal, as is its application in the treatment of malignancy, including determining, in a unique manner, the frequency of modulation resulting in absorption empirically but safely using CT.
The equipment itself consists of a CT scanner and a klystron microwave device, both of established safety and effectiveness. Guidelines for use have also been established including shielding requirements. (The current proposal would not change the penetrating characteristics of the radiation, so that these operating characteristics would still pertain, in particular as regards shielding, which again, are well established.) As the above analysis shows, the proposed combination of these devices exhibits enhanced effectiveness at no cost to safety.
FIG. 1 (FIG. 1 of '006 patent) shows a radiating system 20 including a CT scanner 22 which has been modified, as will be described below. The scanner 22 includes a plurality of x-ray sources 24, of which three are shown by way of example, and a plurality of x-ray detectors 26, of which three are shown by way of example. The sources 24 and the detectors 26 are held in their respective positions by a frame 28 which encircles a subject 30 which is typically a living creature such as a human being or an animal. The sources 24 and the detectors 26 are positioned symmetrically about the subject 30, and are connected electrically to a controller 32 which includes circuitry. In particular, it is noted that each of the sources 24 is connected by two electric lines to the controller 32, a first of the lines 34 providing an electric signal which activates the source 24, and a second of the electric lines 36 providing an electric signal which modulates the x-ray beam at a predetermined modulation frequency. The detectors 26 are connected by electric lines 38 to the controller 32 for inputting data about detected radiation to the controller 32.
FIG. 2 (FIG. 2 of '006 patent) shows details in the construction of one of the sources 24, as well as components of the controller 32, and an interconnection between the controller 32 and one of the detectors 26. All of the sources 24 function in the same manner, and all of the detectors 26 function in the same manner. The x-ray source 24 comprises a target 40 rotated by a motor 42, and a collimator 44. The collimator is positioned along a path of x-rays emanating from the target 40 for defining an x-ray beam 46 directed towards the subject 30. The source 24 further comprises an electron gun 48 which includes a filament 50 and an electrode assembly 52. The filament 50 is used to emit electrons which are accelerated by electric potentials on the electrode assembly 52 and the target 40 relative to the filament 50, the accelerated electrons forming a beam 54. Electrons of the beam 54 strike the target 40 to generate the x-rays, the process of generation of the x-rays being well-known. A battery 56 connected between the target 40 and the filament 50 symbolically illustrates electric potential in the range of thousands of volts applied between the target 40 and the filaments 50. Electric potential for the electrode assembly 52 is provided from a bias voltage source 58 within the controller 32, the voltage of the source 58 being coupled to the electrode assembly 52 via a switch 60 also located within the controller 32.
The x-ray source 24 further comprises a klystron 62 of which two cavities 64 and 66 are shown in longitudinal sectional view, the cavity 64 being located between the cavity 66 and the electrode assembly 52. The central axis of the klystron 62 coincides with an axis of the electron beam 54. The beam 54 passes through an aperture 68 in an end wall 70 of the cavity 64, a tubular region 72 interconnecting the cavities 64 and 66, and an aperture 74 in an end wall 76 of the cavity 66. A probe 78 in the form of a loop is located in the cavity 64 for receiving inputted microwave power. Microwave power is provided by way of a microwave signal generated within a microwave source 80 located within the controller 32, the microwave signal being coupled from the source 80 to the probe 78 via a switch 82 also located within the controller 32.
Also included within the controller 32 is a computer 84, a frequency selector 86, an analog-to-digital converter 88 and a switch 90. Signals from a detector 26 are coupled by the switch 90 to the converter 88, the converter 88 converting the analog signals of the detector to digitally formatted signals to be inputted to the computer 84.
FIG. 3 (FIG. 6 of the '006 patent) illustrates a basic radiotherapy method. The procedure begins with a modulation of the x-ray beam with the microwave signal. The beam is directed upon the subject and the microwave modulating signal is swept in frequency. The radiation propagating from the x-ray source and through the subject is detected. This is followed by a recording of the frequencies at which absorption of radiant energy occurs. After this information has been obtained, the x-ray beam is modulated at a specific frequency for which absorption has been noted. Then, the beam while modulated at the specific absorption, or resonant, frequency is directed at the subject for irradiating the subject. Photon energy is transferred to macromolecules within the subject for destruction of the macromolecules. Where the macromolecules represent a malignancy, the procedure of the invention destroys the malignancy without damaging neighboring tissue.
The following prior art describe known initial therapeutic achievements and frequency specific biological effects of microwaves
1. Frequency Specific Absorption by DNA, RNA, Protein and Invivo
Webb and Booth3 performed microwave spectroscopy on DNA, RNA, protein, and bacteria, showing individual frequency-specific absorption peaks for each substance which correspond to those of intact cells, with the intensity of absorption at each peak being proportional to the relative proportion of those substances in the cell.
Furthermore, there were frequency specific effects on growth rate of the cells, all corresponding with absorption peaks in the spectra (those of DNA inhibiting growth, those of RNA at one peak inhibiting and at one stimulating growth).
In a review for the Naval Research Institute, Glaser and Dodge19 reported that microwaves between 40 and 150 GHz were found to selectively interfere with the synthesis of DNA and protein, and that the effect appeared to be frequency dependent. Lower frequencies did not show nonthermal mutagenic effects.
2. Differential Absorption by Tumors at Specific Frequencies
Webb4, using laser-Raman spectroscopy, demonstrated that tumor cells absorb microwaves at specific frequencies not absorbed by normal cells and could selectively alter the metabolism of tumor cells in a nonthermal manner by exposure to frequencies harmless to normal cells, all effects being frequency specific.
3. Narrow Resonant Effects of Microwaves on Growth of Cells
Grundler and Keilmann5 found that microwaves influence the growth of yeast with a surprisingly strong frequency dependence, with resonance as narrow as 8 megahertz, confirming the existence of a non-thermal resonant microwave sensitivity in cells. The sharp frequency dependence and effect at low intensity of radiation are indicative of a non-thermal action6. Webb and Dodds18 also detected decreased growth of E. Coli with 136 GCmicrowaves.
4. Frequency Specific Genetic and Viral Destruction
Mickey and colleagues7 demonstrated non-thermal biological effects of high frequency radio waves, including frequency-specific killing of viruses and microorganisms without affecting the host, genetic changes at specific loci, chomosomal aberrations, lethal mutations, and frequency specific denaturation.
A Soviet study20 using millimeter waves was reported to show maximal effect pealing at 6.5 MM., resulting in decreased viral infective activity, increased phage activity. Cell wall disruption, protoplasmic degeneration, altered red blood cell stability, altered nucleic acid and protein concentration, and effects on hematopoiesis and liver cell nuclei and mitochondria.
Viral multiplication in mammalian cells was affected by microwaves as a result of changes in nucleic acid and protein synthesis, resulting in lowered multiplication of herpes virus in infected cells, as reported by Luczak, et al17.
5. Selective Destruction of Tumor by Microwaves
West and Regelson8 noted reduction in tumor size and significantly reduced viability of lung tumor cells and leukemia cells with no lethality of normal embryo cells at low levels of pulsed nonthermal irradiation at 27.12 MHz.
6. Specific Microwave Effects on Chromosomes and DNA
Baranski and Czersk9 noted chromosomal effects and influence of microwave radiation on mitosis, with depressed cell proliferation and chromosomal despirilization, a picture never seen in ionizing radiation induced damage. They felt this indicated with high probability that molecular effects that influence the spatial structure, energy levels, and consequently, the biological and metabolic activity of macromolecules are responsible for these effects in contrast to electrical field changes. Optical Density studies by Varma and Traboulay14 showed DNA strand separation in the GHz range of microwave non-ionizing radiation.
Together, these studies indicate that the frequencies of resonant absorption decrease with increasing molecular size, 100 MHz affecting T-RNA, while millimeter waves affect macromolecular proteins, for example. Similar effects were noted by Revzin and Neumann12, who detected conformation changes in ribosomal-RNA using pulsed MHz radiation, with changes in orientation of the entire RNA molecule concomitant with helix coil transitions of oligomeric base-pair regions, suggesting restructuring of units the size of genes or their transcripts.
7. Mechanism of Action of Microwaves on DNA
Considering the interaction of electromagnetic energy with living systems in the light of quantum effects, Baranski and Czersk9 note that if the photon energy of irradiation corresponds to quantum differences among the various possible energetic states of a molecule, a quantum of energy may be absorbed and excitation of the molecule occurs. Return to the unexcited state may take place by energy transfer by rearrangements within the molecule. Thus, fluctuations from the equilibrium distribution of tertiary structure (e.g. denaturation) are expected.
8. Enhanced Effect of X-Rays Combined with Microwaves
Averbach, et al13, observed decreased growth of E. Coli bacteria at specific microwave frequencies of 70.5 and 73 GHz and reported on a possible interaction with X-rays.
Mickey and Colleagues7 showed that microwave-range waves acting in conjunction with Gamma rays are far more mutagenic than either type of radiation alone.
Frequency specific effects of microwave radiation have been described by Kainer and Frazer10 by Raman spectroscopy, and in a review by Frolich11 describing resonant effects on growth of bacteria, yeast, viruses, protein, metabolism, and alterations in the effects of x-rays on bone marrow.
9. Some Characteristics of the Glutathione Cycle Revealed by Ionizing and Non-Ionizing Electromagnetic Radiation
Holt J A, Med Hypotheses 1995 October; 45(4):345-68 Microwave Therapy Centre, West Perth, Australia.
The cyclic reaction of GSH-->GSSG-->GSH (designated R(exp) or R(e)) obeys the three specific features of life by producing energy in exponential quantities relative to time, is in effect irreversible and is inherited from generation to generation. In multicellular life, this reaction produces the energy for mitosis and is kept in controlled inactivity until needed to maintain perfection of form and function by energizing mitosis. The immediate control of Re appears to be feedback process-dependent on the concentration of GSSG. Ultra high-frequency electromagnetic radiation of 434 MHz (UHF) will change Re from inactive to active and, in so doing, it causes resonance and/or fluorescence of the glutathione cycle which changes its radio sensitivity. Re is the primary direct target of ionizing radiation and produces the energy for mitosis. Clinical observations suggest that, in the normal cell, Re is inactive and is not killed by 3×2700 rads or 6×1650 rads yet, when active, its sensitivity value (DO) is approximately 160 rads. Using the standard radiobiological equation of response to ionizing radiation, it can be deduced that radiosensitive cancers have two or three Re units active per cell and radio resistance increases in proportion to the number of potentially active Re units per cell. Re appears to be the main cause of cancers' increased conductivity of electricity compared with normal tissue. In cancer therapy, UHF is the best radiosensitiser ever discovered (up to two or more decades). Re is also intelligent compared with non-exponential reactions but cannot be the basis of intellectual brain functions which must be based on non-electrical chemical processes.
PMID: 8577298 [PubMed—indexed for MEDLINE]